The overall objective of this proposal is to develop localized water suppressed H-1 NMR spectroscopy into a clinically-useful tool to improve or complement diagnosis, treatment planning, and especially monitoring of the therapy response of osteosarcoma of the human leg and arm. The specific aims of this proposal are: 1) to determine if localization and water suppression techniques can be applied both to implanted osteosarcomas in mice and to osteosarcomas in humans; 2) to determine if viable tumor can be distinguished from normal tissue and necrosis by H-1 NMR in mice and in humans; 3) to determine if the response to tissue and chemotherapy in mice and in humans can be detected and quantified by changes in the H-1 spectrum; 4) to correlate the localized H-1 spectral data from humans with MRI and CT, and, even more importantly, with histopathology and the long-term survival of the patient; and 5) to determine if the H-1 spectral data can differentiate non-responders from responders and do so earlier than with MRI or CT. The following experimental methods are to be used: 1) A surface coil and a Faraday shield will be used for localization of implanted osteosarcomas in mice. Existing localization techniques on the 1.5T GE Signa whole body imager will be evaluated and (if necessary) modified to obtain well-localized H-1 spectra in humans. Various techniques will be evaluated on the mice and the humans to obtain satisfactory water suppression and quantifiable spectral data. 2) Localized spectra of the tumor will be referenced to the histopathology in the mice. Spectra of the tumor, necrosis, and surrounding normal tissue will be referenced to the MR images in the humans. 3) Periodic spectra of the tumor in mice, before and after a single dose of chemotherapy, will be correlated with the volume estimate by calipers. The pre-biopsy H-1 spectral data from humans will be correlated with MRI and CT, the volume estimate, and the-histopathology of the biopsy material. 4) Changes in spectral data will be documented during the course and following chemotherapy. These changes will be compared with imaging data, tumor volume estimates, gross and microscopic histopathology, tumor response to therapy, and the long-term survival of the patient.